Synthesis and evaluation of phosphoramidate amino acid-based inhibitors of sialyltransferases

Bioorg Med Chem Lett. 2003 Jan 20;13(2):301-4. doi: 10.1016/s0960-894x(02)00735-7.

Abstract

Several phosphoramidate analogues of CMP-N-acetylneuraminic acid were prepared for evaluation as inhibitors of alpha-2,3- and alpha-2,6-sialyltransferase. Central to the synthesis was the oxidative coupling of an amino acid ester with an H-phosphonate to construct the phosphoramidate linkage. All compounds synthesized were weak inhibitors of both of the sialyltransferases as determined by an HPLC-based inhibition assay.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carbohydrate Sequence
  • Chromatography, High Pressure Liquid
  • Cytidine Monophosphate / analogs & derivatives*
  • Cytidine Monophosphate / chemical synthesis
  • Cytidine Monophosphate / pharmacology
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Kinetics
  • Molecular Sequence Data
  • Sialyltransferases / antagonists & inhibitors*
  • Spectrophotometry, Ultraviolet

Substances

  • Enzyme Inhibitors
  • Sialyltransferases
  • Cytidine Monophosphate